JP6695908B2 - ベンズアミド化合物の製造方法 - Google Patents
ベンズアミド化合物の製造方法 Download PDFInfo
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- JP6695908B2 JP6695908B2 JP2017565960A JP2017565960A JP6695908B2 JP 6695908 B2 JP6695908 B2 JP 6695908B2 JP 2017565960 A JP2017565960 A JP 2017565960A JP 2017565960 A JP2017565960 A JP 2017565960A JP 6695908 B2 JP6695908 B2 JP 6695908B2
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- -1 benzamide compound Chemical class 0.000 title claims description 85
- 238000004519 manufacturing process Methods 0.000 title claims description 62
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 86
- 239000000126 substance Substances 0.000 claims description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- 239000007864 aqueous solution Substances 0.000 claims description 17
- 239000003054 catalyst Substances 0.000 claims description 17
- 150000003936 benzamides Chemical class 0.000 claims description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 150000008064 anhydrides Chemical group 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 4
- AETDZYWAZLSIRJ-UHFFFAOYSA-N C12(CC3CC(CC(C1)C3)C2)C1=C(C(=O)OC(C2=C(C=CC=C2)C23CC4CC(CC(C2)C4)C3)=O)C=CC=C1 Chemical compound C12(CC3CC(CC(C1)C3)C2)C1=C(C(=O)OC(C2=C(C=CC=C2)C23CC4CC(CC(C2)C4)C3)=O)C=CC=C1 AETDZYWAZLSIRJ-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229910052725 zinc Inorganic materials 0.000 claims description 4
- 239000011701 zinc Substances 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 241000257303 Hymenoptera Species 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 230000035484 reaction time Effects 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000008901 benefit Effects 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- VLLNJDMHDJRNFK-UHFFFAOYSA-N adamantan-1-ol Chemical compound C1C(C2)CC3CC2CC1(O)C3 VLLNJDMHDJRNFK-UHFFFAOYSA-N 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000005711 Benzoic acid Substances 0.000 description 7
- 235000010233 benzoic acid Nutrition 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- GPVDHNVGGIAOQT-UHFFFAOYSA-N 2,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 6
- WDLDXQVTSRCDMN-UHFFFAOYSA-N 5-(1-adamantyl)-n-[(2,4-dihydroxyphenyl)methyl]-2,4-dimethoxybenzamide Chemical compound COC1=CC(OC)=C(C23CC4CC(CC(C4)C2)C3)C=C1C(=O)NCC1=CC=C(O)C=C1O WDLDXQVTSRCDMN-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 230000002087 whitening effect Effects 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- IUNJCFABHJZSKB-UHFFFAOYSA-N 2,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(O)=C1 IUNJCFABHJZSKB-UHFFFAOYSA-N 0.000 description 4
- UIAFKZKHHVMJGS-UHFFFAOYSA-N 2,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1O UIAFKZKHHVMJGS-UHFFFAOYSA-N 0.000 description 4
- GMPRDASKQVWTCP-UHFFFAOYSA-N 5-(1-adamantyl)-2,4-dimethoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(OC)=C1C1(C2)CC(C3)CC2CC3C1 GMPRDASKQVWTCP-UHFFFAOYSA-N 0.000 description 4
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003377 acid catalyst Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- RPUFERHPLAVBJN-UHFFFAOYSA-N n,n-dihydroxy-1-phenylmethanamine Chemical compound ON(O)CC1=CC=CC=C1 RPUFERHPLAVBJN-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- BJJYHNCUAZNAOP-UHFFFAOYSA-N 4-(aminomethyl)benzene-1,3-diol Chemical compound NCC1=CC=C(O)C=C1O BJJYHNCUAZNAOP-UHFFFAOYSA-N 0.000 description 2
- YIAZXUFZAYNWTP-UHFFFAOYSA-N 4-(hydroxyiminomethyl)benzene-1,3-diol Chemical compound ON=CC1=CC=C(O)C=C1O YIAZXUFZAYNWTP-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
- MRIXVKKOHPQOFK-UHFFFAOYSA-N 4-methoxysalicylic acid Chemical compound COC1=CC=C(C(O)=O)C(O)=C1 MRIXVKKOHPQOFK-UHFFFAOYSA-N 0.000 description 2
- CPPPOEUQYCKODN-UHFFFAOYSA-N 5-(1-adamantyl)-2,4-dihydroxybenzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C23CC4CC(CC(C4)C2)C3)=C1O CPPPOEUQYCKODN-UHFFFAOYSA-N 0.000 description 2
- DHXXJPGHCYCRET-UHFFFAOYSA-N 5-(1-adamantyl)-n-[(2,4-dihydroxyphenyl)methyl]-2,4-dihydroxybenzamide Chemical compound OC1=CC(O)=CC=C1CNC(=O)C1=CC(C23CC4CC(CC(C4)C2)C3)=C(O)C=C1O DHXXJPGHCYCRET-UHFFFAOYSA-N 0.000 description 2
- SQCLSKGGXIWWPU-UHFFFAOYSA-N 5-(1-adamantyl)-n-[(2,4-dihydroxyphenyl)methyl]-2-hydroxy-4-methoxybenzamide Chemical compound C1=C(C23CC4CC(CC(C4)C2)C3)C(OC)=CC(O)=C1C(=O)NCC1=CC=C(O)C=C1O SQCLSKGGXIWWPU-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical group C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 229940114055 beta-resorcylic acid Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 125000005926 1,2-dimethylbutyloxy group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- IXWOUPGDGMCKGT-UHFFFAOYSA-N 2,3-dihydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1O IXWOUPGDGMCKGT-UHFFFAOYSA-N 0.000 description 1
- PTNIWJWNLJDPEI-UHFFFAOYSA-N 2,4-dimethoxybenzamide Chemical compound COC1=CC=C(C(N)=O)C(OC)=C1 PTNIWJWNLJDPEI-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- VZJJKOFBPFBBMX-UHFFFAOYSA-N 2-(1-adamantyl)benzoic acid Chemical class OC(=O)C1=CC=CC=C1C1(C2)CC(C3)CC2CC3C1 VZJJKOFBPFBBMX-UHFFFAOYSA-N 0.000 description 1
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- RONMMFGIZUQAPP-UHFFFAOYSA-N 3-(1-adamantyl)-4-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC=C(O)C(C23CC4CC(CC(C4)C2)C3)=C1 RONMMFGIZUQAPP-UHFFFAOYSA-N 0.000 description 1
- MZAJLDVRKVEVKU-UHFFFAOYSA-N 3-(1-adamantyl)-n-[(2,4-dihydroxyphenyl)methyl]-4-methoxybenzamide Chemical compound C1=C(C23CC4CC(CC(C4)C2)C3)C(OC)=CC=C1C(=O)NCC1=CC=C(O)C=C1O MZAJLDVRKVEVKU-UHFFFAOYSA-N 0.000 description 1
- YFUQHJDAFYOKPS-UHFFFAOYSA-N 3-(1-adamantyl)-n-[2-(4-hydroxyphenyl)ethyl]-4-methoxybenzamide Chemical compound C1=C(C23CC4CC(CC(C4)C2)C3)C(OC)=CC=C1C(=O)NCCC1=CC=C(O)C=C1 YFUQHJDAFYOKPS-UHFFFAOYSA-N 0.000 description 1
- HMHNTHVBKCIMNN-UHFFFAOYSA-N 4,4-dihydroxycyclohexa-1,5-diene-1-carboxylic acid Chemical compound OC1(CC=C(C(=O)O)C=C1)O HMHNTHVBKCIMNN-UHFFFAOYSA-N 0.000 description 1
- BHKPCZYOXAVZDF-UHFFFAOYSA-N 4-(aminomethyl)benzene-1,3-diol;hydrochloride Chemical compound Cl.NCC1=CC=C(O)C=C1O BHKPCZYOXAVZDF-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- DPOBUZSKFZQTGB-UHFFFAOYSA-N 5-(1-adamantyl)-2,4-dihydroxy-n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC(C23CC4CC(CC(C4)C2)C3)=C(O)C=C1O DPOBUZSKFZQTGB-UHFFFAOYSA-N 0.000 description 1
- HFSUQKBSCRUCDZ-UHFFFAOYSA-N 5-(1-adamantyl)-2-hydroxy-n-[2-(4-hydroxyphenyl)ethyl]-4-methoxybenzamide Chemical compound C1=C(C23CC4CC(CC(C4)C2)C3)C(OC)=CC(O)=C1C(=O)NCCC1=CC=C(O)C=C1 HFSUQKBSCRUCDZ-UHFFFAOYSA-N 0.000 description 1
- URTMLGDFZCLNEJ-UHFFFAOYSA-N 5-(1-adamantyl)-n-[2-(4-hydroxyphenyl)ethyl]-2,4-dimethoxybenzamide Chemical compound COC1=CC(OC)=C(C23CC4CC(CC(C4)C2)C3)C=C1C(=O)NCCC1=CC=C(O)C=C1 URTMLGDFZCLNEJ-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- JKQSZZXTSBXBCZ-UHFFFAOYSA-N C12(CC3CC(CC(C1)C3)C2)C=1C(=CC(=C(C(=O)OC(C2=C(C=C(C(=C2)C23CC4CC(CC(C2)C4)C3)OC)OC)=O)C=1)OC)OC Chemical compound C12(CC3CC(CC(C1)C3)C2)C=1C(=CC(=C(C(=O)OC(C2=C(C=C(C(=C2)C23CC4CC(CC(C2)C4)C3)OC)OC)=O)C=1)OC)OC JKQSZZXTSBXBCZ-UHFFFAOYSA-N 0.000 description 1
- QIHNNARVYUNQPP-UHFFFAOYSA-N COC1=C(C(=O)O)C=CC(=C1)OC.C12(CC3CC(CC(C1)C3)C2)C=2C(=CC(=C(C(=O)O)C2)OC)OC Chemical compound COC1=C(C(=O)O)C=CC(=C1)OC.C12(CC3CC(CC(C1)C3)C2)C=2C(=CC(=C(C(=O)O)C2)OC)OC QIHNNARVYUNQPP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- UHNWOJJPXCYKCG-UHFFFAOYSA-L magnesium oxalate Chemical compound [Mg+2].[O-]C(=O)C([O-])=O UHNWOJJPXCYKCG-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/75—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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|---|---|---|---|
| KR20150092704 | 2015-06-30 | ||
| KR10-2015-0092704 | 2015-06-30 | ||
| KR1020160067409A KR102622104B1 (ko) | 2015-06-30 | 2016-05-31 | 벤조산아미드 화합물의 제조 방법 |
| KR10-2016-0067409 | 2016-05-31 | ||
| PCT/KR2016/005914 WO2017003107A1 (ko) | 2015-06-30 | 2016-06-03 | 벤조산아미드 화합물의 제조 방법 |
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| Publication Number | Publication Date |
|---|---|
| JP2018519288A JP2018519288A (ja) | 2018-07-19 |
| JP6695908B2 true JP6695908B2 (ja) | 2020-05-20 |
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| JP2017565960A Active JP6695908B2 (ja) | 2015-06-30 | 2016-06-03 | ベンズアミド化合物の製造方法 |
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| Country | Link |
|---|---|
| US (1) | US10723693B2 (de) |
| EP (1) | EP3318550B1 (de) |
| JP (1) | JP6695908B2 (de) |
| KR (1) | KR102622104B1 (de) |
| CN (1) | CN108137485B (de) |
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| CN113620832B (zh) * | 2020-05-07 | 2024-08-13 | 鲁南制药集团股份有限公司 | 一种非布司他中间体的制备方法 |
| CN115304585A (zh) * | 2022-08-23 | 2022-11-08 | 江苏恒沛药物科技有限公司 | 一种阿伐那非的制备方法 |
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| KR100286421B1 (ko) | 1998-08-27 | 2001-04-16 | 김용규 | 고지혈증 치료 화합물의 개선된 제조방법 |
| KR100502833B1 (ko) | 2002-03-25 | 2005-07-25 | 보령제약 주식회사 | 심바스타틴 및 이의 중간체 화합물들의 개선된 제조방법 |
| KR100680584B1 (ko) | 2005-08-19 | 2007-02-08 | (주)아모레퍼시픽 | 히드록시벤즈아미드 화합물 및 그 제조방법, 및 이를유효성분으로 함유하는 화장료 조성물 |
| KR101219281B1 (ko) * | 2005-10-31 | 2013-01-08 | (주)아모레퍼시픽 | 젠티식산 유도체 화합물과 그 제조방법 및 이를 함유하는미백화장료 조성물 |
| CN101602687A (zh) * | 2008-06-13 | 2009-12-16 | 上海特化医药科技有限公司 | 6-硝基苯乙酮类化合物、其制备方法及用途 |
| CN102382076B (zh) * | 2010-09-03 | 2016-08-17 | 中国医学科学院药物研究所 | 芳酮和芳酰胺类化合物及其制法和药物用途 |
| KR101826747B1 (ko) * | 2011-06-30 | 2018-02-08 | (주)아모레퍼시픽 | 신규한 코지산 유도체, 이의 제조 방법 및 이를 유효성분으로 함유하는 피부 미백용 조성물 |
| KR101604053B1 (ko) | 2011-08-05 | 2016-03-16 | (주)아모레퍼시픽 | 신규 벤조산아미드 화합물 |
| CN104370793B (zh) | 2014-01-24 | 2017-10-17 | 中国海洋大学 | 吡咯类海洋生物碱Neolamellarin A类似物及其制备方法和应用 |
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- 2016-05-31 KR KR1020160067409A patent/KR102622104B1/ko active IP Right Grant
- 2016-06-03 US US15/736,406 patent/US10723693B2/en active Active
- 2016-06-03 EP EP16818140.2A patent/EP3318550B1/de active Active
- 2016-06-03 JP JP2017565960A patent/JP6695908B2/ja active Active
- 2016-06-03 CN CN201680038015.4A patent/CN108137485B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US10723693B2 (en) | 2020-07-28 |
| US20180179146A1 (en) | 2018-06-28 |
| CN108137485B (zh) | 2020-11-24 |
| KR20170003387A (ko) | 2017-01-09 |
| EP3318550A1 (de) | 2018-05-09 |
| KR102622104B1 (ko) | 2024-01-09 |
| JP2018519288A (ja) | 2018-07-19 |
| EP3318550A4 (de) | 2018-06-06 |
| EP3318550B1 (de) | 2020-03-04 |
| CN108137485A (zh) | 2018-06-08 |
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